Dataset Information

Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.

ABSTRACT: Retinoid X receptors are members of the nuclear receptor family that regulate gene expression in response to retinoic acid and related ligands. Group 1 metabotropic glutamate receptors are G-protein coupled transmembrane receptors that activate intracellular signaling cascades in response to the neurotransmitter, glutamate. These two classes of molecules have been studied independently and found to play important roles in regulating neuronal physiology with potential clinical implications for disorders such as depression, schizophrenia, Parkinson's and Alzheimer's disease. Here we show that mice lacking the retinoid X receptor subunit, RXR?, exhibit impairments in group 1 mGluR-mediated electrophysiological responses at hippocampal Schaffer collateral-CA1 pyramidal cell synapses, including impaired group 1 mGluR-dependent long-term synaptic depression (LTD), reduced group 1 mGluR-induced calcium release, and loss of group 1 mGluR-activated voltage-sensitive currents. These animals also exhibit impairments in a subset of group 1 mGluR-dependent behaviors, including motor performance, spatial object recognition, and prepulse inhibition. Together, these observations demonstrate convergence between the RXR? and group 1 mGluR signaling pathways that may function to coordinate their regulation of neuronal activity. They also identify RXR? as a potential target for the treatment of disorders in which group 1 mGluR signaling has been implicated.

SUBMITTER: Upreti C

PROVIDER: S-EPMC7946894 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.

Upreti Chirag C Woodruff Caitlin M CM Zhang Xiao-Lei XL Yim Michael J MJ Zhou Zhen-Yu ZY Pagano Andrew M AM Rehanian Dina S DS Yin Deqi D Kandel Eric R ER Stanton Patric K PK Nicholls Russell E RE

Scientific reports 20210310 1

Retinoid X receptors are members of the nuclear receptor family that regulate gene expression in response to retinoic acid and related ligands. Group 1 metabotropic glutamate receptors are G-protein coupled transmembrane receptors that activate intracellular signaling cascades in response to the neurotransmitter, glutamate. These two classes of molecules have been studied independently and found to play important roles in regulating neuronal physiology with potential clinical implications for di ...[more]

PMID: 33692389

Similar Datasets

Project description:BackgroundImpaired muscle regeneration and increased muscle fibrosis are observed in aged muscle accompanied by progressive loss of muscle mass (sarcopenia). However, the underlying mechanism is still unclear.MethodsThe differentiated expressed genes in young and aged muscles after acute injury by cardiotoxin were identified by RNA-sequence analysis. Single-cell RNA-sequence analysis was used to identify cell clusters and functions in young muscle after acute injury, and flow cytometry analysis and sorting were used to validate the function. The proliferation and differentiation functions of satellite cells were accessed by immunostaining with 5-ethynyl-2'-deoxyuridine and embryonic myosin heavy chain (eMyHC), respectively. Muscle regeneration ability was accessed by histopathological and molecular biological methods.ResultsGene expression patterns associated with responses to interferon-gamma (IFN-γ) (15 genes; false discovery rate < 0.001) were significantly down-regulated during muscle regeneration in aged mice (P = 2.25e-7). CD8+ T cells were the main source of increased IFN-γ after injury, adoptive transfer of wild-type CD8+ T cells to IFN-γ-deficient young mice resulted in 78% increase in cross-sectional areas (CSAs) of regenerated myofibres (P < 0.05) and 63% decrease in muscle fibrosis (P < 0.05) after injury. Single-cell RNA-sequence analysis identified a novel subset of macrophages [named as IFN-responsive macrophages (IFNRMs)] that specifically expressed IFN-responsive genes (Ifit3, Isg15, Irf7, etc.) in young mice at 3 days after injury, and the number of this macrophage subset was ~20% lower in aged mice at the same time (P < 0.05). IFNRMs secreted cytokine C-X-C motif chemokine 10 (CXCL10) that promoted the proliferation and differentiation of satellite cells via its receptor, CXCR3. Intramuscular recombinant CXCL10 treatment in aged mice rejuvenated the proliferation of satellite cells (80% increase in Ki-67+ Pax7+ cells, P < 0.01) and resulted in 27% increase in CSA of regenerated myofibres (P < 0.01) and 29% decrease in muscle fibrosis (P < 0.05).ConclusionsOur study indicates that decline in IFN-γ response in a novel subset of macrophage contributes to satellite cells dysfunctions in aged skeletal muscles and demonstrates that this mechanism can be targeted to restore age-associated myogenesis.

Dataset Information

Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.

Publications

Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets